Fulvestrant and Ipatasertib for Advanced HER-2 Negative and Estrogen Receptor Positive (ER+) Breast Cancer Following Progression on First Line CDK 4/6 Inhibitor and Aromatase Inhibitor (FINER)

Double-Blind Placebo-Controlled Randomized Phase III Trial of Fulvestrant and Ipatasertib as Treatment for Advanced HER-2 Negative and Estrogen Receptor Positive (ER+) Breast Cancer Following Progression on First Line CDK 4/6 Inhibitor and Aromatase Inhibitor

The purpose of this study is to find out whether a new drug, Ipatasertib, can slow the growth of advanced breast cancer when added to standard therapy (Fulvestrant).

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Ipatasertib; Drug: Fulvestrant; Other: Placebo

Detailed Description

Patients enrolled in this study will receive either Ipatasertib plus Fulvestrant or placebo (a substance that looks like the study drug but does not have any active or medicinal ingredient) plus Fulvestant. The study will provide information about the ability of Ipatasertib plus Fulvestrant to control the cancer, the side effects and safety of the treatment, how patients feel while taking the treatment and associated costs.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Wendy Parulekar; Phone Number: 613-533-6430; Email: wparulekar@ctg.queensu.ca

Study Locations

• Australia
  • Garran, Australia, ACT 2605
    • Suspended
    • Canberra Hospital
  • Herston, Australia, 4029
    • Suspended
    • Royal Brisbane and Womens Hospital
  • New South Wales
    • Bowral, New South Wales, Australia, 2576
      • Suspended
      • Southern Highlands Cancer Centre
    • Gateshead, New South Wales, Australia, 2324
      • Suspended
      • Lake Macquarie Private Hospital
    • Gosford, New South Wales, Australia, 2250
      • Suspended
      • Gosford Hospital
    • Macquarie University, New South Wales, Australia, 2109
      • Recruiting
      • Macquarie University Hospital
      • Contact: Dhanusha Sabanathan
    • Nowra, New South Wales, Australia, 2541
      • Suspended
      • Shoalhaven Cancer Care Centre
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Suspended
      • Sunshine Coast University Hospital
    • Toowoomba, Queensland, Australia, 4350
      • Recruiting
      • Toowoomba Hospital
      • Contact: Bhaskar Karki
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
      • Suspended
      • Victorian Breast and Oncology Care
    • Epping, Victoria, Australia, 3076
      • Suspended
      • The Northern Hospital
    • Frankston, Victoria, Australia, 3199
      • Recruiting
      • Frankston Hospital
      • Contact: Jacqui Thomson; Phone Number: 3 5976-0812
    • Melbourne, Victoria, Australia, 3004
      • Not yet recruiting
      • Alfred Hospital
      • Contact: Maggie Moore
    • St. Albans, Victoria, Australia, 3021
      • Suspended
      • Sunshine Hospital
  • Western Australia
    • Bunbury, Western Australia, Australia, 6230
      • Suspended
      • St John of God Bunbury
    • Murdoch, Western Australia, Australia, 6150
      • Suspended
      • Fiona Stanley Hospital
• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • Suspended
      • BCCA - Cancer Centre for the Southern Interior
    • Surrey, British Columbia, Canada, V3V 1Z2
      • Suspended
      • BCCA - Fraser Valley Cancer Centre
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Recruiting
      • BCCA - Vancouver Cancer Centre
      • Contact: Stephen Chia; Phone Number: 2752 604 877-6000
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Not yet recruiting
      • Regional Health Authority B, Zone 2
      • Contact: Margot Burnell; Phone Number: 506 648-6884
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Recruiting
      • QEII Health Sciences Centre
      • Contact: Daniel Rayson; Phone Number: 902 473-6106
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Suspended
      • Royal Victoria Regional Health Centre
    • Brampton, Ontario, Canada, L6R 3J7
      • Recruiting
      • William Osler Health System
      • Contact: Margaret Balcewicz; Phone Number: 572643 905 494-2120
    • Hamilton, Ontario, Canada, L8V 5C2
      • Suspended
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 2V7
      • Suspended
      • Kingston Health Sciences Centre
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • London Regional Cancer Program
      • Contact: Jacques Antoun Raphael; Phone Number: 519 685-8640
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Suspended
      • Stronach Regional Health Centre at Southlake
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • Ottawa Hospital Research Institute
      • Contact: Terry Ng; Phone Number: 613 737-7700
    • Sault Ste. Marie, Ontario, Canada, P6B 0A8
      • Suspended
      • Algoma District Cancer Program
    • Thunder Bay, Ontario, Canada, P7B 6V4
      • Suspended
      • Thunder Bay Regional Health Sciences Centre/
    • Toronto, Ontario, Canada, M5G 2M9
      • Suspended
      • University Health Network
    • Windsor, Ontario, Canada, N8W 2X3
      • Suspended
      • Windsor Regional Cancer Centre
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Suspended
      • Centre Integre de Sante et de Services Sociaux
    • Montreal, Quebec, Canada, H2X 3E4
      • Recruiting
      • CHUM-Centre Hospitalier de l'Universite de Montreal
      • Contact: Jean-Pierre Ayoub; Phone Number: 20692 514 890-8000
    • Quebec City, Quebec, Canada, G1S 4L8
      • Suspended
      • CHA-Hopital Du St-Sacrement
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Suspended
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Suspended
      • Saskatoon Cancer Centre
• New Zealand
  • Auckland, New Zealand, 1023
    • Suspended
    • Auckland City Hospital
  • Wellington, New Zealand, 2
    • Suspended
    • Wellington Cancer Centre, Wellington Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically and/or cytologically confirmed ER positive, HER-2 negative breast cancer
• Female patients must be post-menopausal; female patients who are pre-menopausal must have ovarian suppression using LHRH agonist while on study
• Clinical and/or radiographic progression during treatment with or within 28 days after discontinuation of first line of treatment with a CDK 4/6 inhibitor and an aromatase inhibitor (AI) for advanced/metastatic disease
• Evidence of clinically and/or radiologically documented disease
• ≥ 18 years of age
• ECOG performance status of 0 or 1

• No concurrent anti-cancer therapy and must satisfy the following criteria for previous therapy

  • Must not have received more than one prior line of treatment with a CDK 4/6 inhibitor and an AI in the advanced disease setting.
  • Treatment with CDK 4/6 inhibitor and AI must have been the most recent treatment prior to registration for this study

• Adequate hematology and organ function, in the absence of growth factors

  • Absolute neutrophils > 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Hemoglobin > 90 g/L
  • Total Bilirubin ≤ 1.5 x ULN (upper limit of normal) or ≤ 3 x ULN if confirmed Gilbert's Syndrome
  • ALT and AST ≤ 2.5 x ULN (or ≤ 5.0 x ULN if liver or bone metastasis)
  • Alkaline phosphatase ≤ 2.0 x ULN (or ≤ 5.0 x ULN if liver metastases, ≤ 7.0 x ULN if bone metastasis)
  • Fasting glucose ≤ 8.3 mmol/L
  • HbA1c ≤ 7.5%
  • Serum albumin ≥ 30 g/L
  • INR ≤ 1.2
  • Serum Creatinine or Creatinine clearance ≤ 1.5 x ULN or ≥ 50 mL/min; measured directly by 24-hour urine sampling or as calculated by Crockcroft and Gault equation

Exclusion Criteria:

• Untreated or symptomatic CNS metastases, radiation treatment for CNS metastases within 28 days
• Active inflammatory bowel disease, bowel inflammation, inability to swallow oral medication or GI condition that alters oral absorption
• Prior treatment with fulvestrant, selective estrogen receptor degraders (SERDs) or known inhibitors of the PI3K pathway including PI3K inhibitors, AKT inhibitors, or mTOR inhibitors
• Mean QT interval corrected for heart rate (QTc) ≥ 480 msec by ECG or history of familial long QT syndrome
• Active or uncontrolled infections or serious illnesses or medical conditions
• Clinically significant liver diseases
• History of lung disease or history of opportunistic infections
• Type 1 or Type 2 diabetes mellitus requiring insulin
• Grade ≥ 2 uncontrolled hypercholesterolemia or hypertriglyceridemia
• Known abnormalities in coagulation
• History of hypersensitivity to the study drugs or components
• Pregnant or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Fulvestrant; 500 mg IM cycle 1 days 1 and 15 followed by 500 mg IM day 1 q 28 days subsequent cycles; Other: Placebo; PO QD days 1-21 every 28 days
Experimental: Ipatasertib + Fulvestrant	Drug: Ipatasertib; 400 mg PO QD days 1-21 every 28 days; Drug: Fulvestrant; 500 mg IM cycle 1 days 1 and 15 followed by 500 mg IM day 1 q 28 days subsequent cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival (PFS) using RECIST 1.1	5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	5 years
To compare the two treatment arms with respect to investigator assessed PFS (per RECIST 1.1) in the PIK3CA/AKT1/PTEN altered cohort	5 years
Investigator assessed PFS (per RECIST 1.1) in the PIK3CA/AKT1/PTEN non-altered cohort	5 years
PFS as assessed by blinded central radiology review in all enrolled patients, PIK3CA/AKT1/PTEN altered and non-altered cohorts	5 years
Response rate (RR) (per RECIST 1.1)	5 years
Duration of Response (DoR)	5 years
Clinical Benefit Rate (CBR);	5 years
Time to commencement of subsequent line of systemic therapy or death (TSST)	5 years
Number of participants with treatment-related adverse events as assessed by CTCAE version 5.0	5 years
Quality of Life (QOL) as measured using EORTC QLQ-C30 questionnaire	5 years
Adverse events as measured using NCI PRO-CTCAE questionnaire	5 years
Economic Evaluation of healthcare utilization using average cost per study subject by treatment arm to estimate an overall mean cost per study arm.	5 years
Economic Evaluation of health utilities measured using EQ-5D-5L	5 years

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Collaborators: Hoffmann-La Roche
• Investigators: Study Chair: Stephen Chia, BCCA - Vancouver Cancer Centre, BC Canada

Study record dates

Study Major Dates

• Study Start (Actual): January 27, 2021
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 24, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (Actual): December 2, 2020

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protein Kinase Inhibitors; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Fulvestrant; Ipatasertib
• Other Study ID Numbers: MA40; 2101 (Other Identifier: BCT); M041883 (Other Identifier: Hoffmann-LaRoche Ltd.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No